The 3p14.2 to p21.1 region of human chromosome 3 is estimated to contain between 10 and 15 megabases of DNA. The major goal of this proposal is to construct a cohesive, high resolution physical map for this region which is defined by two translocations. The familial renal cell carcinoma translocation, t(3;8)(p14.2;q24.1), marks the proximal boundary while the distal boundary is marked by a t(3;7)(p21.1;p13) translocation present in hereditary Grieg- polysyndactyly syndrome, a developmental disorder. The map will be constructed using nine cloned DNA hybridization probes that have been regionally localized to this interval in addition to other clones to be isolated. Pulsed field gel electrophoresis of high molecular weight genomic DNA coupled with Southern blot analysis will be used to construct long range restriction endonuclease cleavage maps around each probe. Maps surrounding additional clones will be constructed as these clones are isolated and regionally localized. Clones that contain clusters of rare-cutting restriction endonuclease cleavage sites (HTF island clones) will be especially useful for mapping, but all clones in the region will be utilized. The nine clones available now should generate maps that cover between 50% and 100% of the region, depending upon clone distribution. The individual maps will be connected into one comprehensive map by searching for overlapping patterns of restriction endonuclease cleavage sites in addition to analysis of partial digests on pulsed field gel Southern blots. The map constructed should be useful for identifying locations of potential genes (at HTF islands) and for defining the deletions and translocations that commonly affect this chromosomal region in malignant diseases such as renal cell carcinoma and small cell lung carcinoma, among others. Extension of this map into the surrounding chromosomal regions on the proximal and distal sides should be relatively straightforward. This map should provide a foundation upon which a comprehensive map of the entirety of chromosome 3 can be built.